JP6359175B2 - ＰＡＲＰ阻害剤としての４Ｈ‐ピラゾロ［１，５‐α］ベンゾイミダゾール化合物のアナログ - Google Patents

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Publication number

JP6359175B2

JP6359175B2 JP2017504223A JP2017504223A JP6359175B2 JP 6359175 B2 JP6359175 B2 JP 6359175B2 JP 2017504223 A JP2017504223 A JP 2017504223A JP 2017504223 A JP2017504223 A JP 2017504223A JP 6359175 B2 JP6359175 B2 JP 6359175B2

Authority

JP

Japan

Prior art keywords

group

fluoro

imidazo

benzo

formamide

Prior art date

2014-04-10

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

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• 239000012661 PARP inhibitor Substances 0.000 title description 3
• 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 title description 3
• 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title description 3
• 150000001875 compounds Chemical class 0.000 claims description 223
• -1 cyclopropylmethylene group Chemical group 0.000 claims description 160
• 229910052794 bromium Inorganic materials 0.000 claims description 64
• 229910052801 chlorine Inorganic materials 0.000 claims description 64
• 229910052731 fluorine Inorganic materials 0.000 claims description 63
• 229910052740 iodine Inorganic materials 0.000 claims description 62
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 56
• ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 54
• 125000001424 substituent group Chemical group 0.000 claims description 52
• 150000003839 salts Chemical class 0.000 claims description 50
• 229910052739 hydrogen Inorganic materials 0.000 claims description 42
• 125000005842 heteroatom Chemical group 0.000 claims description 38
• 125000000217 alkyl group Chemical group 0.000 claims description 36
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 34
• 125000000623 heterocyclic group Chemical group 0.000 claims description 33
• 229910052757 nitrogen Inorganic materials 0.000 claims description 33
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 31
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 29
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 21
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 20
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 20
• 125000004404 heteroalkyl group Chemical group 0.000 claims description 19
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 19
• 229910052799 carbon Inorganic materials 0.000 claims description 17
• 229910052717 sulfur Inorganic materials 0.000 claims description 16
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 15
• 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 14
• 125000005257 alkyl acyl group Chemical group 0.000 claims description 14
• 239000003814 drug Substances 0.000 claims description 14
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 14
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 14
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 13
• 229910052760 oxygen Inorganic materials 0.000 claims description 13
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 11
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 10
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 9
• 125000002252 acyl group Chemical group 0.000 claims description 9
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 9
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 9
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 9
• 125000005149 cycloalkylsulfinyl group Chemical group 0.000 claims description 9
• 125000003545 alkoxy group Chemical group 0.000 claims description 8
• 125000003282 alkyl amino group Chemical group 0.000 claims description 8
• 125000003277 amino group Chemical group 0.000 claims description 8
• 125000004122 cyclic group Chemical group 0.000 claims description 8
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 8
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 7
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
• 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 6
• 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 6
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• 206010028980 Neoplasm Diseases 0.000 claims description 6
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 6
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 6
• 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 6
• 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 6
• 229940124597 therapeutic agent Drugs 0.000 claims description 6
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
• ITYPIHCCBGIXLG-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCNCC2)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2(CCNCC2)C)C=1)C(=O)N ITYPIHCCBGIXLG-UHFFFAOYSA-N 0.000 claims description 5
• 125000005144 cycloalkylsulfonyl group Chemical group 0.000 claims description 5
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
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• CCVUCMOLANHVOS-UHFFFAOYSA-N C(C)N1C2CC(CC1CC2)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(C)N1C2CC(CC1CC2)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F CCVUCMOLANHVOS-UHFFFAOYSA-N 0.000 claims description 4
• HQQQWHXBTUIYAN-UHFFFAOYSA-N C(C)N1CCC(CC1)C1=C2N(N=C1)C1=C(N2C)C=C(C=C1C(=O)N)F Chemical compound C(C)N1CCC(CC1)C1=C2N(N=C1)C1=C(N2C)C=C(C=C1C(=O)N)F HQQQWHXBTUIYAN-UHFFFAOYSA-N 0.000 claims description 4
• YHHFHJNIDHVKNO-UHFFFAOYSA-N C(C)N1CCC(CCC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C(C)N1CCC(CCC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F YHHFHJNIDHVKNO-UHFFFAOYSA-N 0.000 claims description 4
• LJCHPPRPLKQHRU-UHFFFAOYSA-N C(C1=CC=CC=C1)COC=1C(=C2N(N1)C1=C(N2)C=C(C=C1C(=O)N)F)C1(CCN(CC1)C(C)C)C Chemical compound C(C1=CC=CC=C1)COC=1C(=C2N(N1)C1=C(N2)C=C(C=C1C(=O)N)F)C1(CCN(CC1)C(C)C)C LJCHPPRPLKQHRU-UHFFFAOYSA-N 0.000 claims description 4
• SCOCNPKTLCOFBW-UHFFFAOYSA-N C1(CC1)CN1CCC(CC1)(C)C1=C2N(N=C1C)C1=C(N2)C=C(C=C1C(=O)N)F Chemical compound C1(CC1)CN1CCC(CC1)(C)C1=C2N(N=C1C)C1=C(N2)C=C(C=C1C(=O)N)F SCOCNPKTLCOFBW-UHFFFAOYSA-N 0.000 claims description 4
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• PIIRUXFKGRLZDK-UHFFFAOYSA-N CCN1CCC(CC1)C1=C2C(O)C3=CC(F)=CC(C(N)=O)=C3N2N=C1 Chemical compound CCN1CCC(CC1)C1=C2C(O)C3=CC(F)=CC(C(N)=O)=C3N2N=C1 PIIRUXFKGRLZDK-UHFFFAOYSA-N 0.000 claims description 4
• UJJFHEWKNDQARH-UHFFFAOYSA-N CN(C1CCC(CC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F)C Chemical compound CN(C1CCC(CC1)C1=C2N(N=C1)C1=C(N2)C=C(C=C1C(=O)N)F)C UJJFHEWKNDQARH-UHFFFAOYSA-N 0.000 claims description 4
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• TWVGTRDBBKNOEZ-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C(=O)N2CCN(CC2)C)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C(=O)N2CCN(CC2)C)C=1)C(=O)N TWVGTRDBBKNOEZ-UHFFFAOYSA-N 0.000 claims description 4
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• KADJYYQDTBEPQS-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2=CC=C(C=C2)C2CNCCC2)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2=CC=C(C=C2)C2CNCCC2)C=1)C(=O)N KADJYYQDTBEPQS-UHFFFAOYSA-N 0.000 claims description 4
• GNYABDRZRWYLCZ-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2=CC=C(C=C2)F)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2=CC=C(C=C2)F)C=1)C(=O)N GNYABDRZRWYLCZ-UHFFFAOYSA-N 0.000 claims description 4
• WMAWWVKHXNYCGN-UHFFFAOYSA-N FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CC2)CC(C)(C)F)C=1)C(=O)N Chemical compound FC=1C=C(C2=C(NC=3N2N=CC=3C2CCN(CC2)CC(C)(C)F)C=1)C(=O)N WMAWWVKHXNYCGN-UHFFFAOYSA-N 0.000 claims description 4
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• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
• 206010012601 diabetes mellitus Diseases 0.000 claims description 4
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 4
• 230000004054 inflammatory process Effects 0.000 claims description 4
• 208000031225 myocardial ischemia Diseases 0.000 claims description 4
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 4
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